title: Vasomotor dysfunction in the mesenteric artery after organ culture with cyclosporin A.
abstract: Cyclosporin A (CsA) is a widely used immunosuppressive agent that also causes hypertension. However, the molecular basis for CsA-induced hypertension remains elusive. In this study, we established an in vitro model for CsA-induced pathological changes in vasculature. Rat mesenteric arteries were incubated with CsA for 24 hr in an organ culture system. Both vasocontraction and vasorelaxation in mesenteric artery were studied using myograph technology, and mRNA expressions of the contractile receptors were determined by real-time PCR. The results showed that CsA increased the mRNA expression and contractile function of several G-protein-coupled receptors (GPCRs), such as endothelin receptor type B (ETB ), 5-hydroxytryptamine type 1B (5-HT1B ) and 1D (5-HT1D ), in vascular smooth muscle cells. In addition, both nitric oxide (NO)-mediated vasorelaxation and endothelium-independent relaxation were impaired by CsA. In summary, this study showed the enhanced GPCRs-mediated contraction and reduced vasorelaxation in mesenteric artery after organ culture with CsA, which mimicked the CsA-induced pathological changes in the vascular system in vivo. Furthermore, this organ culture system would be an ideal in vitro tool to study the molecular mechanisms of CsA-induced hypertension.
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Jian-Pu
authors.initials: JP
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Zhuoan
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Peng
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D014757:Viper Venoms; C057354:sarafotoxins s6; D016572:Cyclosporine